Abstract The pediatric and adult transplant programs at Duke University Medical Center have served as a core clinical center for the BMT-CTN since its establishment in 2001. As a core center, Duke has made significant contributions to the network, including enrollment of 310 patients on CTN protocols, chairing two protocols (Dr. Kurtzberg chaired 0501 and Dr. Horwitz chaired 0901); serving on 6 protocol committees and 2 disease committees, authoring manuscripts and establishing and managing the immune reconstitution core for protocol 0501. The center has been in compliance with accurate and timely data and bio-specimen submission. The PI and Co-PI have regularly attended steering committee meetings, conference calls and the SSOS meetings. For this renewal of the BMT-CTN, Duke brings three specialized types of expertise to the table, (1) a long- standing and pioneering role in cord blood transplantation and banking and (2) unique experience in the treatment of pediatric patients with hematopoietic stem cell transplantation for non-malignant diseases and (3) pioneering work in cord blood and cord-tissue derived cellular therapies. In this application, Duke has added two additional centers as part of a Duke Consortium to increase participation in the network and also to increase accrual to BMT-CTN trials. The study concept proposed in this application, will serve as the foundation for a follow-on study to BMT-CTN 0501. The clinical trial proposed will compare in a randomized phase II clinical trial, the outcomes of related haplo-identical bone marrow transplantation or unrelated donor cord blood transplantation in children with high risk leukemias undergoing myeloablative conditioning therapy. The supportive care will be standardized. The preparative regimens and GvHD prophylaxis will be based on treatment `packages' well studied for the cord blood group and piloted for the haplo-BMT group. They are standardized to the extent possible, with the splitting cyclophosphamide for pre and post-transplant dosing for the haplo group and use of fludarabine in the cord blood group. The primary endpoint will be relapse-free survival at 2 years post-transplant. Overall survival, engraftment, acute and chronic Graft-versus-Host Disease, treatment related mortality, immune reconstitution, and transplant feasibility will also be explored as secondary endpoints. The predictive role of MRD at the time of transplant will also be examined to determine if either graft source offers better protection against post- transplant leukemic relapse. This study will answer critical and timely questions about the role of various alternative donors and identification of best practices for alternative donor selection for transplantation of children with hematological malignancies lacking matched related or unrelated donors. We plan to fund this trial by responding to the FOA Clinical Coordinating Center for Multi-Site Investigator- Initiated Clinical Trials (Collaborative UG3/UH3) PAR-16-300, which is due on February 13, 2017. Dr. Mary Eapen, from the CIBMTR, will serve as the PI for the grant application for the Data Coordinating Center which will utilize the infra-structure already established for the BMT-CTN. We have full support of the group at Johns Hopkins who developed the haplo post-transplant cyclophosphamide approach, The CIBMTR and the pediatric transplant community to conduct this study and prioritize accrual to the trial. Accordingly, we expect to accrue 180 patients in 3-4 years and, with two-year follow-up and data analysis, expect to complete the study in <6 years.